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Failure to prevent secondary infectious complications in acute necrotizing pancreatitis (ANP) is attributable in part to the limited penetration of antimicrobial drugs. As newer quinolones are particularly attractive owing to their antimicrobial activity, for the first time we studied the penetration of moxifloxacin into pancreatic tissue in patients.In this prospective, non-comparative clinical trial, 60 patients undergoing elective pancreas resection received a single oral or intravenous (iv) dose of 400 mg moxifloxacin for perioperative antimicrobial prophylaxis. The concentration of moxifloxacin was measured in samples taken from blood and from pancreatic tissue at the beginning and at the end of resection.Mean moxifloxacin concentrations in pancreatic tissue following iv or oral administration were 3.1 ± 0.9 and 2.7 ± 1.4 mg/kg at 3–3.7 h post-dose (first sampling) and 3.6 ± 1.5 and 3.1 ± 1.8 mg/kg at 4.3–5.3 h post-dose (second sampling), respectively. Corresponding mean plasma concentrations of moxifloxacin were 1.8 ± 0.5 and 1.2 ± 0.6 mg/L (first sampling) and 1.5 ± 0.4 and 1.0 ± 0.5 mg/L (second sampling), respectively. From first to second sampling, the mean tissue-to-plasma ratios varied from 1.8 ± 0.6 to 2.6 ± 1.2 (iv) and from 2.4 ± 0.8 to 3.1 ± 1.2 (oral). Pancreatic tissue concentrations of moxifloxacin exceeded the MIC90 for the relevant pathogens covered by moxifloxacin for at least 5 h after dosing.Moxifloxacin has been demonstrated to penetrate efficiently into human pancreatic tissue following iv or oral administration. From a pharmacological perspective, moxifloxacin appears to be promising for prophylaxis and treatment of local pancreas infections. Whether it is beneficial in the prevention and therapy of infectious complications in patients with ANP should be investigated in a controlled clinical trial.